2FES

Orally active thrombin inhibitors

2FES の概要

• エントリーDOI: 10.2210/pdb2fes/pdb
• 関連するPDBエントリー: 1O0D
• 関連するBIRD辞書のPRD_ID: PRD_000480 PRD_000613
• 分子名称: Thrombin light chain, Thrombin heavy chain, Decapeptide Hirudin Analogue, ... (5 entities in total)
• 機能のキーワード: thrombin inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted, extracellular space: P00734 P00734
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 35854.95

構造登録者

Hoeffken, H.W. (登録日: 2005-12-16, 公開日: 2006-05-09, 最終更新日: 2023-08-30)

主引用文献

Mack, H.,Baucke, D.,Hornberger, W.,Lange, U.E.W.,Seitz, W.,Hoeffken, H.W.
Orally active thrombin inhibitors. Part 1: optimization of the P1-moiety.
Bioorg.Med.Chem.Lett., 16:2641-2647, 2006

PubMed Abstract: The synthesis and SAR of novel nanomolar thrombin inhibitors with the common backbone HOOC-CH(2)-d-cyclohexylalanyl-3,4-dehydroprolyl-NH-CH(2)-aryl-C(=NH)NH(2) are described together with their ecarin clotting time (ECT) prolongation as measure for thrombin inhibition ex vivo. The aryl P1-moiety mimicking the arginine part of the d-Phe-Pro-Arg derived thrombin inhibitors turned out to be a key component for in vitro potency and in vivo activity. Optimization of this part led to compounds with improved antithrombin activity in rats and dogs after oral administration compared to the recently launched anticoagulant melagatran.

PubMed: 16517159
DOI: 10.1016/j.bmcl.2006.02.040

実験手法

X-RAY DIFFRACTION (2.42 Å)